Phillygenin glucuronic acid derivative as well as preparation method and application thereof

Abstract

The present invention provides a novel phillygenin glucuronic acid derivative shown as a general formula (I). wherein, R 1 =H, R 2 =C n H 2n+1 , R 3 =C n H 2n+1 or R 1 =C n H 2n+1 , R 2 =C n H 2n+1 ,R 3 =H or R 1 -R 2 =—CH 2 —, R 3 =C n H 2n+1 ; n=1-30. The present invention further relates to a preparation method of the compound, a pharmaceutical composition taking the compound as an active ingredient, as well as application of the compound in the present invention in antiviral diseases.

The invention claimed is: 
     
       1. A preparation method of a phillygenin glucuronic acid derivative, the method sequentially comprises the following steps:
 1) mixing forsythia leaves and extraction solvent water and heating, decocting and extracting for 2-3 times, and collecting and merging the extracting solution, and thereby obtaining a forsythia water extract; 
 2) separating the forsythia water extract by adopting a macroporous resin column, and collecting and merging the eluent, and thereby obtaining a forsythia resin column eluent; 
 3) performing silica-gel column chromatography on the forsythia resin column eluent, collecting the eluent at stages, respectively drying the eluent, thereby obtaining the phillygenin glucuronic acid derivative, 
 
       and the phillygenin glucuronic acid derivative comprises a general molecular formula shown as a formula (I): 
       
         
           
           
               
               
           
         
       
       wherein, R 1 =H, R 2 =C n H 2n+1 , R 3 =C n H 2n+1  or R 1 =C n H 2n+1 , R 2 =C n H 2n+1 , R 3 =H or R 1 -R 2 =—CH 2 —, R 3 =C n H 2n+1 ; n=1. 
     
     
       2. The preparation method of  claim 1 , wherein in each decocting process in the step 1), a weight ratio of the forsythia leaves to the extraction solvent water is 1:6-10. 
     
     
       3. The preparation method of  claim 1 , wherein the method further comprises the following steps: concentrating the forsythia water extract in the step 1), preparing a forsythia concentrated solution, and performing macroporous resin column separation treatment. 
     
     
       4. The preparation method of  claim 3 , wherein a ratio of the volume of the forsythia concentrated solution prepared by concentration treatment to the weight of the forsythia leaves is a range from 1:1 to 5:1. 
     
     
       5. The preparation method of  claim 1 , wherein in the step 3), C18 reversed-phase silica-gel serves as packing in the silica-gel column chromatography process; specifications of a chromatographic column comprise an internal diameter of 10-100 mm and a length of 10-300 mm; a particle size of the packing is 5-10 μm; and a mobile phase is eluted in an isocratic elution manner or a gradient elution manner. 
     
     
       6. The preparation method of  claim 5 , wherein the mobile phase in the silica-gel column chromatography process is a mixed solution of methanol and water, wherein a volume ratio of the methanol to the water is 8:2-10:1. 
     
     
       7. A method of treating a human patient in need of treatment for influenza virus infection, wherein the method comprises administering to the patient a phillygenin glucuronic acid derivative, and the phillygenin glucuronic acid derivative comprises a general molecular formula shown as a formula (I): 
       
         
           
           
               
               
           
         
       
       wherein, R 1 =C n H 2n+1 , R 2 =C n H 2n+1 , R 3 H or R 1 -R 2 =—CH 2 —, R 3 =C n H 2n+1 ;n=1-30.